Obesity has become a major public health concern in the United States today. Although the role of increased food intake in the development of obesity has received much attention, little is known concerning factors that determine how much is eaten and how meals are terminated. The feeding behavior of some obese individuals may reflect deficits of satiety, the short-term inhibitory control of meal intake. More over, recent data from animal studies indicate that satiety deficits in the obese may be nutrient specific. The present proposal is designed to investigate the nature and role of satiety deficits in several obese rat models and how they are influenced by the different macronutrients. The possibility that different satiety alterations may occur during the development of obesity, as compared to its maintenance, will also investigated in the proposed research, which has as its long term objective knowledge of the bases of satiety alterations in obesity and the role of specific macronutrients in these alterations. Information obtained from this research may provide insight into the nature of satiety disorders in obese humans, as well as suggest potential modes of treatment. The specific aims of this research are to investigate: 1) macronutrient influences on the satiety behavior of obese rats by determining the satiating effectiveness of intragastric macronutrient infusions; 2) the relation of preabsorptive satiety mechanisms to the enlarged meals of obese rats by evaluating gastric emptying and intestinal absorption of test meals of varied macronutrient composition; 3) the relation of altered nutrient deposition to the feeding behavior of obese rats by examining clearance and uptake of radiolabelled nutrients; and 4) the manner in which the altered satiety of obese rats may be modified with pharmacological agents which influence proposed satiety mechanisms.